TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney

Saskia L. Gooskens, Samantha Gadd, Jaime M. Guidry Auvil, Daniela S. Gerhard, Javed Khan, Rajesh Patidar, Daoud Meerzaman, Qing Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Charles G. Mullighan, Jing Ma, Lawrence J. Jennings, Ronald R. de Krijger, Marry M. van den Heuvel-Eibrink, Malcolm A. Smith, Nicole Ross, Julie M. Gastier-FosterElizabeth J. Perlman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified. One tumor with t(10;17)(q22;p13) involving fusion of YHWAE with NUTM2B was identified. Integrated analysis of expression and methylation data identified promoter hypermethylation and low expression of the tumor suppressor gene TCF21 (Pod-1/capsulin/epicardin) in all CCSKs except the case with t(10;17) (q22;p13). TARID, the long noncoding RNA responsible for demethylating TCF21, was virtually undetectable in most CCSKs. TCF21 hypermethylation and decreased TARID expression were validated in an independent set of CCSK tumor samples. The presence of significant hypermethylation of TCF21, a transcription factor known to be active early in renal development, supports the hypothesis that hypermethylation of TCF21and/or decreased TARID expression lies within the pathogenic pathway of most CCSKs. Future studies are needed to functionally verify a tumorigenic role of TCF21 down-regulation and to tie this to the unique gene expression pattern of CCSK.

Original languageEnglish (US)
Pages (from-to)15828-15841
Number of pages14
Issue number18
StatePublished - 2015


  • Clear cell sarcoma of the kidney
  • Methylation
  • TCF21
  • Whole genome sequencing

ASJC Scopus subject areas

  • Oncology


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